Early detection and accurate measurement of disease allows the maximum likelihood of successful treatment and recovery. Furthermore, early detection and localization of the disease can permit directed therapy to the site of the disease optimizing the efficiency of the treatment. With an appropriate detection device, the treatment can be monitored, further increasing the efficacy of the applied drugs or other forms of therapy. The ability to target specific diseases can also improve treatment outcomes. Early detection and localization of cancer, the second leading cause of death in the US, can improve patient outcomes. Early detection, as used herein, refers to the initial detection of the presence of cancer as well as the detection of metastases, in each case while the tumor or metastases are relatively small or early in their growth process. Early detection also refers to detection of small changes in the size or other characteristics of tumors. Much of the discussion herein refers to in vivo cancer for ease of illustration; the invention is applicable to other biological conditions such as measurement of Amyloid plaque (e.g., by targeting plaque) and characterization of immune system response such as in monitoring transplant status or immunotherapy (e.g., by targeting T cells), as well as ex vivo operation such as in evaluating cell cultures, biopsies, or other tissue samples.
Many common methods used for clinical purposes for detection of cancer are non-specific, i.e., they cannot distinguish between cancerous or benign tumors and none lead to 100% accurate detection. The available methods all have disadvantages and weaknesses, resulting in high rates of false diagnosis and too low a rate of positive diagnosis, together leading to increased mortality rates. The most common clinical modalities presently available are: (1) X-ray mammography, (2) magnetic resonance imaging (MRI), and (3) ultrasound scanning with (4) positron-emission tomography (PET) an additional option when available.
The measurement of X-ray attenuation provides information on the density of the intervening medium. X-rays are FDA approved and are the most common technique used to detect various forms of disease and, in particular, cancer. It is also responsible for many false-negative and false-positive results. Early stage cancer tumors can be detected but without specificity with regard to benign or cancerous tumors. Artifacts can be caused by healthy tissue and give rise to false positive results. Irregularities in tissue such as scarring can cause non-uniform scattering of the x-rays rendering mammograms ineffective. Although the dose is low, there is increasing concern about the exposure to X-rays and radiation in general. Overall, the number of false positives in x-ray imaging of cancer remains high and the x-ray method cannot detect early-stage tumors.
Ultrasound is used to provide a method for imaging tumors. Ultrasound has excellent contrast resolution but suffers from diminished spatial resolution compared to x-rays and other imaging techniques. Ultrasound is non-specific to cancer versus benign tissue. Ultrasound is not currently approved by the FDA as a primary screening tool for cancer but is normally used as a follow up to investigate any abnormalities detected during routine examinations. It is often used to confirm suspect areas in x-ray images of breast and ovarian cancer.
MRI is used to follow up on potential problem areas seen during x-ray scans; however, the expense of a MRI scan often prohibits its use. MRI can detect small abnormalities in tissue and also can be useful in determining if cancer has metastasized. Dynamic Contrast Enhanced (DCE) MRI potentially distinguishes between benign and cancerous tumors but produces a number of false positives. The expense of MRI limits its application as a screening tool. MRI imaging of cancer can use magnetic nanoparticles as contrast agents and is an accepted protocol providing standards for the injection of such nanoparticles. Intravascular MRI contrast agents at a dose of 2 mg/kg of nanoparticle weight have been proposed to detect metastatic lesions. MRI detection of contrast is subjective and relies on the expertise of the physician reading the scans.
Because of the importance of early detection of disease, there are a variety of other techniques currently being studied for imaging. These include scintimammography using PET or SPECT, Impedance Tomography, and various forms of RF imaging.
Early detection of lesions while they are still contained is crucial, since the cure rate of many cancers detected early is near 100%. Existing imaging methods often do not identify lesions until significant growth has occurred. There is ongoing research in alternative methods, including MRI, PET, ultrasound, scintigraphy, and other methods. At present, none of these methods have specificity regarding tumor type using differences in tissue properties between cancerous and non-cancerous tissue. In particular, a new approach not relying on harmful radiation, or very expensive procedures, and offering very early detection of tumors is clearly needed. The present invention provides new capabilities for in-vivo detection and measurement of cancer and other targetable biological substances.